Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Clarke, A; Skerjanz, J; Gsell, MAF; Wiedner, P; Erkan-Candag, H; Groschner, K; Stockner, T; Tiapko, O.
PIP2 modulates TRPC3 activity via TRP helix and S4-S5 linker.
Nat Commun. 2024; 15(1): 5220
Doi: 10.1038/s41467-024-49396-6
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- Führende Autor*innen der Med Uni Graz
- Tiapko Oleksandra
- Co-Autor*innen der Med Uni Graz
- Erkan Candag Hazel
- Groschner Klaus
- Gsell Matthias
- Skerjanz Julia
- Wiedner Patrick
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- Abstract:
- The transient receptor potential canonical type 3 (TRPC3) channel plays a pivotal role in regulating neuronal excitability in the brain via its constitutive activity. The channel is intricately regulated by lipids and has previously been demonstrated to be positively modulated by PIP2. Using molecular dynamics simulations and patch clamp techniques, we reveal that PIP2 predominantly interacts with TRPC3 at the L3 lipid binding site, located at the intersection of pre-S1 and S1 helices. We demonstrate that PIP2 sensing involves a multistep mechanism that propagates from L3 to the pore domain via a salt bridge between the TRP helix and S4-S5 linker. Notably, we find that both stimulated and constitutive TRPC3 activity require PIP2. These structural insights into the function of TRPC3 are invaluable for understanding the role of the TRPC subfamily in health and disease, in particular for cardiovascular diseases, in which TRPC3 channels play a major role.
- Find related publications in this database (using NLM MeSH Indexing)
- TRPC Cation Channels - metabolism, chemistry, genetics
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- Binding Sites - administration & dosage
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- Patch-Clamp Techniques - administration & dosage
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